Hydrochloric Acid → HCID 131731087, compound

HRID 1912373Notes

Reaction equation

HRID 1912373 reaction equation
[NH:1]([C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])[C@H:2]([C:19](O)=[O:20])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:6][CH:5]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:57][C@H:58]([C:63]([O:65][CH3:66])=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61].CCN(C(C)C)C(C)C>C(Cl)Cl.C(OCC)(=O)C>[NH:1]([C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])[C@H:2]([C:19]([NH:57][C@H:58]([C:63]([O:65][CH3:66])=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:20])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:8][CH:9]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 65105(+)-L-Leucine methyl esterHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68183311HCID 68183311, compound

Product 1

HCID 131731087HCID 131731087, compoundYield 101.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cbz-Phe(4-CH2NHBoc)-OH (214 mg, 0.5 mmol, 1 equiv.) was dissolved in DCM. HBTU (228 mg, 0.6 mmol, 1.2 equiv.), HCl.H-Leu-OMe (100 mg, 0.55 mmol, 1.1 equiv.) and DiPEA (0.29 ml, 1.75 mmol, 3.5 equiv.) were added and the mixture was stirred for 2 hours before being concentrated. The residue was dissolved in ethyl acetate (EA) and washed with 1M HCl (2×), sat. aq. NaHCO3 (4×), brine and dried over MgSO4. Column chromatography (tol->30% EA:tol) yielded the title compound (282 mg, 508 μmol, quant.). 1H NMR (400 MHz, CDCl3): δ ppm 7.35-7.22 (m, 5H), 7.19-7.04 (m, 4H), 6.81 (d, J=6.7 Hz, 1H), 5.76 (d, J=8.4 Hz, 1H), 5.16-4.94 (m, 2H), 4.69-4.45 (m, 2H), 4.26-4.11 (m, 2H), 3.67 (s, 3H), 3.13-2.88 (m, 2H), 1.64-1.47 (m, 3H), 1.44 (s, 9H), 0.94-0.81 (m, 6H). 13C NMR (101 MHz, CDCl3): δ ppm 172.83, 170.76, 155.81, 137.23, 136.04, 135.30, 129.37, 128.28, 127.92, 127.70, 127.57, 79.13, 66.70, 55.73, 52.06, 50.51, 44.19, 41.08, 37.94, 28.23, 24.51, 22.52, 21.69.

Workup

  1. concentrationbefore being concentrated
  2. dissolutionThe residue was dissolved in ethyl acetate (EA)
  3. washwashed with 1M HCl (2×), sat. aq. NaHCO3 (4×), brine
  4. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-b2ccf85b67554191a72970aefa01967b
Source dataset
uspto-grants-2013_12
Patent number
US08609610B2

Reaction notes

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